Complement factor H variant Y402H is a major risk determinant for geographic atrophy and choroidal neovascularization in smokers and nonsmokers

Tiina Sepp, Jane C. Khan, Deborah A. Thurlby, Humma Shahid, David G. Clayton, Anthony T. Moore, Alan C. Bird, John R.W. Yates*, Shomi S. Bhattacharya, Paul N. Bishop, Peter D. Black, Zahida A. Butt, Victor N.H. Chong, Nicholas E. Day, Clive Edelsten, Alan W. Fitt, Declan W. Flanagan, Andrew M. Glenn, Simon Harding, Clifford M. JakemanColin D. Jones, Robert J. Lamb, Andrew J. Lotery, Victor Moffatt, Consuela M. Moorman, Tunde Peto, Rajadurai J. Pushpanathan, Elizabeth Redmond, Timothy J. Rimmer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

154 Citations (Scopus)


PURPOSE. The complement factor H (CFH) gene polymorphism Y402H (1277T→C) has been associated with susceptibility to age-related macular degeneration (AMD). The purpose of this study was to confirm this association in a U.K. population, to determine whether the association holds for both geographic atrophy (GA) and choroidal neovascularization (CNV), and to investigate interactions with smoking. METHODS. A case- control study was undertaken in 443 cases of AMD, with 262 spouses as control subjects. All subjects completed a health and lifestyle questionnaire, had an ophthalmic assessment with fundus photography, and were genotyped. RESULTS. The frequencies of the C allele and CC genotype were significantly higher in cases than in controls. In comparison to the TT genotype, the odds ratios for AMD associated with the CT and CC genotypes were 3.1 (CI 2.0 - 4.6) and 6.3 (CI 3.8 -10.4), respectively. The results were similar in subgroup analyses confined to cases with GA or CNV. The findings were also similar for subgroup analyses restricted to subjects who had never smoked, moderate smokers, or heavier smokers (>20 pack years of smoking). Heavier smokers with the CC genotype may be particularly at risk. The frequency of the CC genotype did not differ significantly between cases with and without a family history of AMD. There was no evidence that genotype had any influence on age at onset of disease. CONCLUSIONS. The CFH Y402H variant is strongly associated with both GA and CNV in the U.K. population. This association is similar in smokers and nonsmokers. Heavier smokers with the CC genotype may be at particular risk.

Original languageEnglish
Pages (from-to)536-540
Number of pages5
JournalInvestigative Ophthalmology and Visual Science
Issue number2
Publication statusPublished - 01 Feb 2006
Externally publishedYes

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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